1. Exosomes derived from vMIP-II-Lamp2b gene-modified M2 cells provide neuroprotection by targeting the injured spinal cord, inhibiting chemokine signals and modulating microglia/macrophage polarization in mice.
- Author
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Fu GQ, Wang YY, Xu YM, Bian MM, Zhang L, Yan HZ, Gao JX, Li JL, Chen YQ, Zhang N, Ding SQ, Wang R, Li JY, Hu JG, and Lü HZ
- Subjects
- Animals, Mice, Lysosomal-Associated Membrane Protein 2 metabolism, Lysosomal-Associated Membrane Protein 2 genetics, Cell Polarity drug effects, Cell Polarity physiology, Female, Neuroprotection physiology, Signal Transduction drug effects, Chemokines metabolism, Spinal Cord Injuries pathology, Spinal Cord Injuries metabolism, Spinal Cord Injuries genetics, Exosomes metabolism, Exosomes transplantation, Macrophages metabolism, Microglia metabolism, Microglia drug effects, Microglia pathology, Mice, Inbred C57BL
- Abstract
Inflammation is one of the key injury factors for spinal cord injury (SCI). Exosomes (Exos) derived from M2 macrophages have been shown to inhibit inflammation and be beneficial in SCI animal models. However, lacking targetability restricts their application prospects. Considering that chemokine receptors increase dramatically after SCI, viral macrophage inflammatory protein II (vMIP-II) is a broad-spectrum chemokine receptor binding peptide, and lysosomal associated membrane protein 2b (Lamp2b) is the key membrane component of Exos, we speculated that vMIP-II-Lamp2b gene-modified M2 macrophage-derived Exos (vMIP-II-Lamp2b-M2-Exo) not only have anti-inflammatory properties, but also can target the injured area by vMIP-II. In this study, using a murine contusive SCI model, we revealed that vMIP-II-Lamp2b-M2-Exo could target the chemokine receptors which highly expressed in the injured spinal cords, inhibit some key chemokine receptor signaling pathways (such as MAPK and Akt), further inhibit proinflammatory factors (such as IL-1β, IL-6, IL-17, IL-18, TNF-α, and iNOS), and promote anti-inflammatory factors (such as IL-4 and Arg1) productions, and the transformation of microglia/macrophages from M1 into M2. Moreover, the improved histological and functional recoveries were also found. Collectively, our results suggest that vMIP-II-Lamp2b-M2-Exo may provide neuroprotection by targeting the injured spinal cord, inhibiting some chemokine signals, reducing proinflammatory factor production and modulating microglia/macrophage polarization., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)
- Published
- 2024
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